This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human glycyl-tRNA synthetase, a class II aminoacyl?tRNA synthetase and an essential enzyme of the translational pathway, was found to be associated with a type of inherited neurodisorders in the peripheral nervous systems (PNS) Charcot-Marie-Tooth (CMT) diseases. CMTs represent the most common genetic diseases of the PNS, affecting approximately 1 in 2,500 people. Mutations in the GlyRS gene cause CMT type 2 neuropathies (CMT2D), arising from defects intrinsic to the neuron. The mechanisms of these neurodisorders are not fully understood. To reveal the possible structural impact of the CMT causing mutations, we seek to solve the crystal structures of human GlyRS and the mutants. This would help in understanding the role of GlyRS in CMT disease from the structural perspective.